Stabilized orthosilicic acid comprising preparation and biological preparation

ABSTRACT

A preparation comprising ortho silicic acid which is stabilized with a stabilizing agent and is substantially free of organic silicon compounds, preferably a nitrogen-containing stabilizing agent such as choline, to a method for preparing such a preparation, comprising: i) providing a solution containing a stabilizing agent; ii) dissolving an inorganic silicon compound in the solution containing the stabilizing agent; and iii) hydrolyzing the silicon compound to ortho silicic acid, and to the obtained biological preparation.

This application is a 371 of PCT/NL95/00054, filed on Feb. 7, 1995.

Silicon is an essential trace element for plants, animals and humans. Ina watery environment silicon is initially present as ortho silicic acidwhich is quickly converted by polycondensation to polysilicic acid,which transposes into a colloidal solution and gels. Ultimately,insoluble silicates are formed.

In the same way as carbonic acid for compounds comprising carbon, orthosilicic acid is the most important metabolite for organic siliconcompounds. Water glass (sodium ortho silicate) is the usual source ofortho silicic acid, which however hydrolyses after oral administrationto mammals and forms insoluble and non-absorbable gels throughpolycondensation.

Organic silicon compounds such as alcohol esters, such as ethyl orthosilicate and glycol ortho silicate, cannot be used in biological systemsbecause of the poor solubility and the low resistance to hydrolysis, butabove all because of the unacceptable toxicity.

There therefore exists a need for a silicon-comprising preparation notpossessing the above stated drawbacks, because silicon has a positivebiological effect on nails, hair, skin, teeth, collagen, connectivetissue, bones, encourages cell generation, stimulates the immune systemagainst infections and toxins and inhibits degenerative(ageing)-processes.

The present invention is based on the insight that if ortho silicic acidis formed in the presence of a stabilizing agent, polycondensation isinhibited and even avoided and, furthermore organic silicon compoundssubstantially do not occur.

A first aspect of the present invention therefore relates to apreparation comprising ortho silicic acid which is stabilized with astabilizing agent and is substantially free of organic siliconcompounds.

A second aspect of the present invention relates to a method forpreparing a preparation as according to claims 1-7, which comprises of:

i) providing a solution containing a stabilizing agent;

ii) dissolving an inorganic silicon compound in the solution containingthe stabilizing agent; and

iii) hydrolyzing the silicon compound to ortho silicic acid.

A third aspect of the present invention relates to a biologicalpreparation containing a preparation according to claims 1-7, and/or apreparation prepared according to claims 8-13, and a pharmacologicallyacceptable diluent.

The biological preparation according to the invention is can be usedfor:

chronic infections with destruction of the mucous membranes: forms ofsinusitis and ulcers.

problems with connective tissues, arteriosclerosis, bone and tendonproblems, gynaecology (fibroids, polycystic adenopathy); and

the growth of children: children with recurrent infections with overloadof the lymphatic system.

The stabilization using a stabilizing agent preferably takes place withstabilizing agents containing a nitrogen atom with a free electron pairwhich forms a complex with the silanol groups of the ortho silicic acid.Quaternary ammonium compounds are preferably used, for instancetetra-alkyl compounds, wherein each alkyl group contains for instance1-5 carbon atoms, in particular methyl and ethyl groups. Very highlyrecommended are trialkylhydroxyalkyl compounds, wherein the hydroxygroup is preferably methanol or ethanol. Choline has been found verysuitable, which is further recommended in that it provides the option ofthe stabilizing agent also forming the solution for the ortho silicicacid, and an inert solvent can therefore be omitted.

Another or additional type of stabilizing agent is an amino acid, suchas proline and serine. Serine enhances uptake in the stomach and givesadditional stability.

Starting point for the preparation of the ortho silicic acid-comprisingpreparation is a solution containing the stabilizing agent, wherein aninert solvent can be used. Incorporated in -This solution is aninorganic silicon compound which hydrolysis under the influence of waterto ortho silicic acid, which is immediately stabilized by thestabilizing agent that is present. The solution containing thestabilizing agent can initiate the hydrolysis immediately after additionof the inorganic silicon compound. Usually recommended is a solutioncontaining a stabilizing agent in which no hydrolysis can take placeuntil after the addition of a hydrolyzing agent, such as water.

If choline is used as stabilizing agent it can be converted to cholinehydrochloride using dry hydrochloric acid. In this liquid stabilizingagent can be incorporated the inorganic silicon compound, such as asilicon halogenide, particularly silicon tetrachloride.

Simultaneously with the addition of the inorganic silicon compound, orfollowing the addition of the hydrolyzing agent, the hydrolysis of theinorganic silicon compound to ortho silicic acid takes place. Thesilicic acid formed in situ is subsequently stabilized by forming acomplex with the stabilizing agent. It is of great importance hereinthat the stabilizing agent only forms a complex and does not enter intoa reaction, particularly an esterifying reaction, with the ortho silicicacid. Then achieved is that no organic silicon compounds are createdwhich have an inherent toxicity, are absorbed in the stomach and enterthe blood circulation.

After forming a complex the ortho silicic acid-comprising solution canif desired be partially neutralized by adding a base, such as a lye,particularly sodium hydroxide. Neutralization can take place to a pHsmaller than 4, in particular smaller than 3, in general to a pH lyingin the range of 1-3, whereby any polycondensation of ortho silicic acidis substantially avoided.

If desired, a further purification of the preparation can take place,for instance through absorption of contaminants on active carbon,optionally followed by filtration.

If desired, the content of hydrolyzing agent, particularly water, can bereduced by removing the hydrolyzing agent, for instance throughdistillation, whereby a constant viscosity is achieved if use is made ofcholine as the stabilizer.

Preparations then result with a silicon content generally of 1% byweight, preferably of about 4% by weight, such as 8% by weight. A veryacceptable preparation contains 3-5% by weight of silicon, 70s by weightof choline hydrochloride and the rest water. The pH of this preparationlies within the range 1-3.

Biological preparations can be-manufactured from this preparedpreparation for the purpose of administering ortho silicic acid toplants, animals and humans, whereby the bio-availability of silicon isgreatly improved. The above prepared solution can be administered asbiological preparation as such, for instance as nail tincture. A usageof 0.5 ml of a 2% Si-solution per day for three weeks caused a fungalinfection to disappear (3 patients), where treatment with ketonazols didnot render any improvement. If for instance an edible acid, such asmalic acid, is added a preparation results which is very suitable foradministering to horses.

If a solid carrier is added, for instance cattle feed, cattle feedpellets can be pressed therefrom which contain ortho silicic acid instabilized form for administering silicon to cattle. If sugar/maltose isused as solid carrier, tablets and gels can be formed therefrom.

Through use of a glucuronic acid buffer a preparation on a cream basiscan be formed wherein the pH is less than 4, which creams are suitablefor local cutaneous application.

It will be apparent that all kinds of diluents can be used in order toobtain a preparation for biological application. Such diluents containlower alkanols, such as ethanol, dichloromethane, ethyl acetate,glycerine and polyalcohols.

PREPARATION EXAMPLE

Choline hydrochloride (UCB) is dried under vacuum (100° C./6 hours). Thecholine hydrochloride is treated with dry hydrochloric acid. Siliconhydrochloride (1 mol per mol) is added to the formed choline solution ata temperature which is kept below 40° C.

For hydrolysis, water (ice/ice water) is added to the solution whilecooling, wherein the temperature is held within the range of -20° C. to-30° C.

The solution containing the ortho silicic acid is subsequentlyneutralized by adding sodium hydroxide wherein cooling takes place to atemperature below 0° C. The pH neutralization amounts to about 1.3.

A purification over active carbon is then performed, followed byfiltering off the formed precipitate and the active carbon.

After distillation under vacuum a preparation is obtained which contains3% by weight of silicon, 70% by weight choline hydrochloride and therest water.

FAB/MS with glycerol as liquid matrix provides a spectrum with amolecular cation at M/Z 104 (C⁺) and an MC⁺ adduction at M/Z243/245,typical for chloride isotropy. This spectrum is the same as the spectrumfor choline.

NMR-SPECTRUM OF THE PREPARATION SHOWING CHOLINE/ALCOHOL GROUPS

Element analysis produces 24±2% by weight chlorine and 9±1% by weight N.This points to a ratio of chloride to nitrogen of 1:1.

Neutralization is subsequently carried out to a pH of 2.7-3.0.

The preparation is stable for more than two years when stored at roomtemperature.

FORMULATION EXAMPLES Formulation Example A

The biological preparation contains 3% by weight silicon in the form ofortho silicic acid, 70% by weight choline hydrochloride, the rest waterand a pH of 2.7-3.0. This liquid is suitable for oral and cutaneousadministering.

Formulation Example B

The biological preparation as prepared above is mixed with cattle feedwhich ultimately contains silicon as ortho silicic acid in aconcentration of 0.001-0.005% by weight. This mixture can be pressed topellets which are administered to cattle.

Formulation Example C

The preparation A is mixed with sugar and/or maltose which is pressed totablets containing silicon in the form of ortho silicic acid at acontent of 0.1-0.2% Si by weight.

Formulation Example D

A silicon-comprising cream is prepared as follows. A fat phasecontaining Imwitor 960 (Huls) 7%, Miglyol 812 10%, Softigon 701 (Huls)2%, Marlowet TA 25 (Huls) 2%, Lanette N (Henkel) 4%, Isopropylmyristate3%, a water phase containing Inositol 0.2%, Gluconate buffer 0.05 M, pH3.8 ad 100, Glycerol 10% and the preparation A, as well as a perfume.

The fat phase is melted at 80° C., whereafter the water phase, alsoheated to 80° C., is admixed, followed by cooling. Shortly beforesolidifying, the preparation A and perfume (4 drops) are added. Thecream eventually contains 0.01-0.05% by weight silicon as ortho silicicacid.

Flavourings can be added if desired, for instance by dilution (1:30) ina 0.01 M citrate buffer (pH 3.5-3.8) and by adding a flavouring(raspberry and the like).

I claim:
 1. Preparation comprising ortho silicic acid which isstabilized with at least one silicic acid stabilizing agent containingnitrogen, said at least one silicic acid stabilizing agent further beingselected from the group consisting of a quaternary ammonium stabilizerand an amino acid stabilizer, said composition being substantially freeof organic silicon compounds and further being characterized in thatwhen the stabilized ortho silicic acid is in aqueous solutionpolycondensation of ortho silicic acid is substantially avoided. 2.Preparation as claimed in claim 1, wherein the quaternary ammoniumcompound is a tetra-alkyl ammonium compound.
 3. Preparation as claimedin claim 2, wherein the quaternary ammonium compound is atrialkylhydroxyalkyl ammonium compound.
 4. Preparation as claimed inclaim 3, wherein the quaternary ammonium compound is a choline. 5.Biological preparation containing a preparation as claimed in claim 1 incombination with a pharmacologically acceptable diluent.
 6. Thecomposition according to claim 1, further containing a diluent selectedfrom the group consisting of alkanols and dichloromethane.
 7. Thecomposition according to claim 1, further containing a polyalcholdiluent.
 8. The composition according to claim 7, wherein saidpolyalcohol is selected from the group consisting of glycerol andinositol.
 9. Method for stabilizing an ortho silicic acid with astabilizing agent and thereby preparing a preparation as claimed inclaim 1, which comprises of:i) providing a solution containing a silicicacid stabilizing agent containing nitrogen selected from the groupconsisting of quaternary ammonium stabilizer and an amino acidstabilizer; ii) dissolving an inorganic silicon compound, which iscapable of capable of forming ortho silicic acid, in the solutioncontaining the stabilizing agent; and iii) hydrolyzing the siliconcompound to ortho silicic acid.
 10. Method as claimed in claim 9,wherein the silicon compound is a silicon halogenide.
 11. Method asclaimed in claim 10, wherein the silicon compound is silicontetrachloride.
 12. Method as claimed in claim 11, wherein the solutioncontaining the stabilized ortho silicic acid is brought to a pH lowerthan
 4. 13. Method as claimed in claim 12, wherein the stabilizing agentis a chloride of said stabilizing agent.
 14. Method as claimed in claim13, wherein the solution containing the stabilized ortho silicic acid isconcentrated to a silicon content greater than 1% by weight.